The cutaneous circulation plays an integral role in human thermoregulation. There are intrinsic age-related changes in the dermal matrix, in the cutaneous vessels, and in autonomic control of blood flow, any or all of which may alter the cutaneous vascular response to local and whole-body thermal stresses. Studies performed under Grant AG07004-01 through -05 demonstrated that during heat stress, the increase in skin blood flow (SkBF) and skin vascular conductance per degree C increment in body core temperature is markedly attenuated in healthy active men and women over the age of 55, when compared to 20-30 year- old subjects. This decrement appears to be due to peripheral rather than central (e.g., hypothalamic) age-related changes. However, many questions remain about aging and control of skin blood flow. The human SkBF response to elevated body temperature is unique in that there is a well developed active sympathetic vasodilator system as well as an adrenergic vasoconstrictor system. Under any given set of environmental influences, the balance between these two competing systems determines the net SkBF, yet it is not known which system is altered by the aging process. The local iontophoresis of bretylium tosylate - which eliminates vasoconstrictor influences, and thus allows for the study of the active vasodilator system in the absence of constrictor effects - provides a tool with which to examine the mechanisms underlying the effects of intrinsic aging on control of SkBF. In addition, interventions aimed at increasing thermally-induced vasodilation in older subjects have not been examined. Therefore, the scope of the proposed continuation of Grant AG- 07004 is to systematically study the effects of age on the control of human skin blood flow, and the mechanisms underlying the age- related changes. Specific research hypotheses are as follows: 1) In vivo maximal SkBF decreases with advancing age; 2) The efferent pathway involved in the attenuated vasodilatory response with aging is the active vasodilator system; 3) The age- related decline in SkBF can be attenuated by exercise training; 3a) The mechanism responsible is enhanced vasodilator system activity at a given core temperature; 4) In post-menopausal women, estrogen (E2) replacement therapy increases SkBF at a given core temperature; a) This response is secondary to an E2- induced isotonic hypervolemia.